Treating neoplasms

Abstract

Methods of treating a subject with neoplasm (e.g., mesothelioma) or at risk of developing neoplasm by administering a mevalonate pathway inhibitor such as a nitrogen-containing bisphosphonate are disclosed. Examples of nitrogen-containing bisphosphonates include alendronate, ibandronate, minodronate, neridronate, olpadronate, pamidronate, risedronate, and zoledronate. The methods can further include the administration of a p38 inhibitor. Further disclosed are compositions and kits including a nitrogen-containing bisphosphonate and optionally a p38 inhibitor.

1 . A method of treating a subject with mesothelioma or at risk of developing mesothelioma comprising administering to the subject a nitrogen-containing bisphosphonate. 
   
   
       2 . The method of  claim 1 , wherein the nitrogen-containing bisphosphonate is selected from the group consisting of alendronate, ibandronate, minodronate, neridronate olpadronate, pamidronate, risedronate, and zoledronate. 
   
   
       3 . The method of  claim 1 , wherein the nitrogen-containing bisphosphonate is alendronate. 
   
   
       4 . The method of  claim 3 , wherein the alendronate is administered at a dose of about 0.1 mg/day to about 100 mg/day. 
   
   
       5 . The method of  claim 3 , wherein the alendronate is administered at a dose of up to about 70 mg/day. 
   
   
       6 . The method of  claim 1 , wherein the nitrogen-containing bisphosphonate is pamidronate. 
   
   
       7 . The method of  claim 6 , wherein the pamidronate is administered at a dose of about 0.1 mg/day to about 120 mg/day. 
   
   
       8 . The method of  claim 6 , wherein the pamidronate is administered at a dose of up to about 90 mg/day. 
   
   
       9 . The method of  claim 1 , wherein the nitrogen-containing bisphosphonate is risedronate. 
   
   
       10 . The method of  claim 9 , wherein the risedronate is administered at a dose of about 0.1 mg/day to about 50 mg/day. 
   
   
       11 . The method of  claim 9 , wherein the risedronate is administered at a dose of up to about 30 mg/day. 
   
   
       12 . The method of  claim 1 , wherein the nitrogen-containing bisphosphonate is zoledronate. 
   
   
       13 . The method of  claim 12 , wherein the zoledronate is administered at a dose of about 0.1 mg/day to about 5 mg/day. 
   
   
       14 . The method of  claim 12 , wherein the zoledronate is administered at a dose of up to about 4 mg/day. 
   
   
       15 . The method of  claim 1 , wherein the nitrogen-containing bisphosphonate is administered once per day. 
   
   
       16 . The method of  claim 1 , wherein the nitrogen-containing bisphosphonate is administered in multiple doses. 
   
   
       17 . The method of  claim 1 , further comprising administering to the subject a p38 inhibitor. 
   
   
       18 . The method of  claim 17 , wherein the p38 inhibitor is SB202190. 
   
   
       19 . The method of  claim 17 , wherein the p38 inhibitor is administered at the same time as the nitrogen-containing bisphosphonate. 
   
   
       20 . The method of  claim 1 , further comprising identifying a subject with or at risk of developing mesothelioma prior to the administration step. 
   
   
       21 . A composition comprising a nitrogen-containing bisphosphonate and a p38 inhibitor. 
   
   
       22 . The composition of  claim 21 , wherein the nitrogen-containing bisphosphonate is selected from the group consisting of alendronate, ibandronate, minodronate, neridronate, olpadronate, pamidronate, risedronate, and zoledronate. 
   
   
       23 . The composition of  claim 21 , wherein the nitrogen-containing bisphosphonate is alendronate. 
   
   
       24 . The composition of  claim 21 , wherein the nitrogen-containing bisphosphonate is pamidronate. 
   
   
       25 . The composition of  claim 21 , wherein the nitrogen-containing bisphosphonate is risedronate. 
   
   
       26 . The composition of  claim 21 , wherein the nitrogen-containing bisphosphonate is zoledronate. 
   
   
       27 . The composition of  claim 21 , wherein the p38 inhibitor is SB202190. 
   
   
       28 . A kit comprising a composition comprising a nitrogen-containing bisphosphonate and instructions for administering the composition to a subject with mesothelioma or at risk of developing mesothelioma. 
   
   
       29 . The kit of  claim 28 , wherein the nitrogen-containing bisphosphonate is selected from the group consisting of alendronate, ibandronate, minodronate, neridronate, olpadronate, pamidronate, risedronate, and zoledronate. 
   
   
       30 . The kit of  claim 28 , further comprising a p38 inhibitor. 
   
   
       31 . The kit of  claim 29 , wherein the p38 inhibitor is SB202190.